# The role of type 1 dendritic cells in CD4 and CD8 T cell anti-tumor immunity

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2021 · $31,970

## Abstract

PROJECT SUMMARY
Cancer immunotherapies have revolutionized the treatment of malignancies, but these therapeutics still face
enormous challenges and limited efficacy in many patients. To overcome these limitations, improved strategies
for CD8 T cell-targeted therapies will require increased understanding of how other immune players, particularly
CD4 helper T cells, help in anti-tumor CD8 T cell immunity. CD4 T cells are thought to promote CD8 T cell
responses by CD40-dependent “licensing” of the antigen presenting cells (APCs) that prime CD8 T cells. It is
now clear that CD8 T cells rely almost exclusively on conventional type 1 dendritic cells (cDC1) for priming
against tumor and viral antigens. However, no study has directly identified the APC that primes the CD4 T cells
responsible for licensing or clearly identified cDC1 as the target of CD4 licensing in vivo. The proposed research
elucidates the cellular interactions required for priming anti-tumor CD4 T cells and mediating CD4 help for
augmenting anti-tumor CD8 T cell responses. The overarching hypothesis is that in the setting of tumor-derived
antigens, cDC1 function as an autonomous platform capable of priming both CD4 and CD8 T cells and
orchestrating their crosstalk required for optimal anti-tumor immunity. This will be tested using novel in vivo
genetic models that allow for selective manipulation of molecules in cDC1. Aim 1 of this proposal investigates
the hypothesis that cDC1 directly prime CD4 T cells against tumor-derived antigens. This aim will examine the
effect of antigen form during immunization on CD4 T cell priming in vivo and then compare anti-tumor CD4 T
cells responses in models where MHC class II expression is selectively inactivated or induced on cDC1. Aim 2
investigates the hypothesis that CD4 T cells indirectly provide necessary help for anti-tumor CD8 T cell priming
and checkpoint blockade immunotherapy through CD40 signaling on cDC1. This aim will characterize anti-tumor
CD8 T cell responses and efficacy of checkpoint blockade immunotherapy in tumor-bearing models that
genetically lack CD4 T cell help. It will also define the direct cellular interactions for CD40-dependent help. In the
long term, the proposed work will increase mechanistic understanding of immune interactions against cancers,
which may aid the development of more widely successful immunotherapies and treatments.
This applicant is an MD-PhD candidate at an institution with a long history of supporting physician-scientists at
all stages of their training and is working with a strongly committed mentoring team. The proposed training plan
provides new conceptual and technical training, along with scientific, clinical, and career development activities
that support a trajectory to become an independent physician-scientist focused on discovering mechanisms of
cancer immunology that may be applied to develop novel strategies for therapies.

## Key facts

- **NIH application ID:** 10140994
- **Project number:** 1F30CA247262-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Renee Paula Wu
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,970
- **Award type:** 1
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140994

## Citation

> US National Institutes of Health, RePORTER application 10140994, The role of type 1 dendritic cells in CD4 and CD8 T cell anti-tumor immunity (1F30CA247262-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10140994. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*